The interaction of benzo(a)pyrene (BP) with histone and nonhistone chromosomal proteins (NHCP) will be analyzed. BP will be converted to reactive metabolites employing a NADPH-dependent rat liver microsomal activating system. Initially studies will be carried out with a model target system (calf thymus nuclei) and covalent binding of BP to both histone and NHCP will be characterized utilizing high resolution analytical techniques. Particular attention will be directed at histone 1 (H1), the principal histone target for covalent BP binding. The possible restricted binding distribution of BP to H1 subfractions and the localization of BP in the primary structure of H1 will be examined (utilizing chemical modification and restricted proteolysis techniques). The effect of BP binding on the association of both histones and NHCP with double-stranded DNA will be studied (using affinity chromatography). Subsequent studies will examine BP-chromosomal protein interactions in a transformable cell line and will compare the covalent binding of BP to that of BP 4'5-oxide, a noncarcinogenic analog. The binding of BP also will be compared in transformable vs. a nontransformable cell line and in a transformable cell line at transforming vs. nontransforming doses of carcinogen. It is anticipated that the proposed studies will yield valuable insights into those macromolecular target(s) (interactions) which are essential components of malignant transformation(s) induced by polycyclic aromatic hydrocarbon carcinogens.